Stable pharmaceutical formulations

Abstract

Stable pharmaceutical formulations and methods of making same are provided. In a general embodiment, the present disclosure provides a method of making a stable pharmaceutical formulation comprising adding one or more vitrifying additives to an aqueous pharmaceutical solution to raise the glass transition temperature of the aqueous pharmaceutical solution. The aqueous pharmaceutical solution can be cooled to a temperature of about −50° C. to about −10° C. The vitrifying additive enhances the formation of a glass or amorphous solid of the aqueous pharmaceutical solution at cryogenic temperatures (−50 to −10° C.), and the pharmaceutical formulation can be thawed to liquid form and administered to a mammalian subject.

1. A method of stabilizing a pharmaceutical agent without lyophilization, the method comprising:
 combining a carbapenem with water and a cyclodextrin to form an aqueous carbapenem solution, the cyclodextrin being present in an amount ranging from about 1% to about 30% effective to enhance the formation of an amorphous solid of the aqueous carbapenem solution when the aqueous carbapenem solution is cooled to a temperature below a glass transition temperature of the aqueous carbapenem solution; and 
 cooling the aqueous carbapenem solution to a temperature of about −25° C. to about −10° C. to form the amorphous solid of the aqueous carbapenem solution. 
 
     
     
       2. The method of  claim 1  further comprising aseptically filling the aqueous carbapenem solution in a container before cooling. 
     
     
       3. The method of  claim 1  further comprising storing the cooled aqueous carbapenem solution at a temperature of about −10° C. to about −25° C. for a period of at least about three months. 
     
     
       4. The method of  claim 3  wherein the storing period is at least about six months. 
     
     
       5. The method of  claim 3 , wherein the carbapenem in the aqueous carbapenem solution exhibits less than about ten percent degradation after storing. 
     
     
       6. The method of  claim 3  further comprising thawing the aqueous carbapenem solution and administering the thawed aqueous carbapenem solution to a patient. 
     
     
       7. The method of  claim 6  further comprising the step of diluting the thawed carbapenem solution before administering the solution to a patient. 
     
     
       8. The method of  claim 1 , wherein the carbapenem is unstable in aqueous solution at room temperature. 
     
     
       9. The method of  claim 1 , wherein the cyclodextrin is 2-hydroxypropyl-beta-cyclodextrin. 
     
     
       10. The method of  claim 1 , wherein the solution is ready to use upon thawing. 
     
     
       11. The method of  claim 1 , wherein the solution is a concentrate. 
     
     
       12. The method of  claim 11 , further comprising the step of diluting the concentrate to provide a solution suitable for infusion into a patient.